L-Glutamine Supplementation: Evidence-Based Recommendations
Primary Recommendation
L-glutamine supplementation is NOT recommended for general use in critically ill patients, cancer patients undergoing chemotherapy/radiotherapy, or most hospitalized patients, as recent high-quality evidence shows no mortality benefit and potential harm in certain populations. 1, 2
Specific Clinical Scenarios Where Glutamine MAY Be Beneficial
Parenteral Nutrition in Severe Acute Pancreatitis
- When enteral nutrition is not feasible, parenteral glutamine at 0.20 g/kg/day should be supplemented, as it reduces infectious complications, mortality, and hospital stay in patients requiring total parenteral nutrition. 3
- This represents one of the few scenarios with consistent evidence supporting glutamine use. 3
Surgical Patients on Exclusive Parenteral Nutrition
- Parenteral glutamine (0.35-0.5 g/kg/day) may be considered ONLY for surgical patients who cannot be fed enterally and require exclusive PN. 2
- This is a weak recommendation due to mixed evidence, with the largest trials showing no effect on surgical morbidity or mortality. 3, 2
- One meta-analysis found only a modest reduction in hospital length of stay. 3
Clinical Scenarios Where Glutamine Is NOT Recommended or Contraindicated
Critical Illness with Multi-Organ Failure
- Do NOT use glutamine in critically ill patients with multi-organ failure or organ dysfunction—it is associated with INCREASED mortality. 2, 4
- The Society of Critical Care Medicine explicitly reports increased mortality with high-dose glutamine in this population. 2
Cancer Treatment
- ESPEN states there are insufficient consistent clinical data to recommend glutamine during conventional cytotoxic therapy, targeted therapy, or radiotherapy. 1, 3, 2
- The Multinational Association of Supportive Care in Cancer (MASCC) and International Society for Oral Oncology (ISOO) recommend AGAINST intravenous glutamine for preventing oral mucositis in patients receiving high-dose chemotherapy. 3
- Major safety concern: Glutamine is metabolized at high rates by cancer cells and has been associated with higher tumor relapse rates in hematopoietic stem cell transplantation patients. 3
Acute Kidney Injury or Chronic Kidney Disease
- The National Kidney Foundation recommends AGAINST high-dose parenteral glutamine in acute kidney injury or chronic kidney disease with kidney failure. 2
Radiation-Induced Complications
- There are insufficient consistent clinical data to recommend glutamine to prevent radiation-induced enteritis/diarrhea, stomatitis, esophagitis, or skin toxicity. 1
The Evolution of Glutamine Evidence: Why Recommendations Changed
Historical Context
- Early meta-analyses and small studies suggested mortality reduction and decreased infectious complications with glutamine supplementation. 1, 5, 6
- The hypothesis that glutamine becomes "conditionally essential" during critical illness led to widespread recommendations for supplementation. 1, 5
Recent High-Quality Evidence Changed the Landscape
- The glutamine story is over in the sense that the hypothesis that ALL critically ill patients should receive glutamine has been demonstrated to be invalid. 1
- Recent large, well-designed studies failed to show mortality benefit in primary analyses. 1
- The 2012 Surviving Sepsis Campaign guidelines noted that although previous meta-analyses showed mortality reduction, four subsequent meta-analyses did not confirm this benefit. 1
- Indiscriminate use of glutamine supplementation in critically ill patients may actually cause harm rather than beneficial effects. 1
Route of Administration Matters
- Beneficial effects were found mostly in trials using parenteral rather than enteral glutamine. 1
- Studies involving patients on enteral nutrition with enterally administered supplementation are less likely to show beneficial effects. 1
- However, even recent well-sized studies with parenteral glutamine could not demonstrate reduction of infectious complications or organ dysfunction. 1
Dosing Considerations (When Appropriate)
Parenteral Route
- Severe acute pancreatitis: 0.20 g/kg/day 3
- Surgical patients on exclusive PN: 0.35-0.5 g/kg/day 2
- HSCT patients (per ASPEN): approximately 0.6 g/kg/day 2 (though ESPEN states insufficient evidence 2)
Enteral Route
- High-dose enteral glutamine (≥30 g/day) was used in older studies, but current evidence does not support routine use. 5
Monitoring and Safety Considerations
Plasma Glutamine Levels
- Low plasma glutamine concentration at ICU admission is an independent mortality predictor. 1
- The hypothesis that SOME critically ill patients may have hypoglutaminemia requiring correction has not been tested appropriately. 1
- Most patients will normalize plasma glutamine concentration by adding 20-25 g/24 hours. 6
Contraindications and Cautions
- Severe liver disease: Use with caution due to glutamine's role in ammonia metabolism. 4
- Patients with significant comorbidities, particularly liver or kidney disease. 4
- Avoid high-dose supplementation in all patients. 2, 4
Common Pitfalls to Avoid
Do not extrapolate older meta-analyses to current practice—the most recent large trials show no benefit or potential harm. 1
Do not assume enteral glutamine has the same effects as parenteral—route of administration significantly influences outcomes. 1
Do not use glutamine as a general immune-modulating supplement—there is no sign of clear benefit in clinical trials for this purpose. 1
Do not supplement glutamine in cancer patients based on theoretical benefits—the risk of tumor stimulation is a major unresolved safety issue. 3
Do not ignore organ dysfunction status—glutamine in multi-organ failure is associated with increased mortality. 2